This proposal seeks to identify the pathophysiologic mechanisms involved in autoimmune thrombocytopenic purpura (AITP) and determine how they are affected by treatment. Hypoproliferative thrombopoiesis may be a previously unrecognized, major component of the thrombocytopenia in AITP patients. Factors that influence platelet life-span (antibody-mediated increased platelet removal, platelet-endothelial cell interactions, and the status of the RE system) are of only secondary importance in determining the circulating platelet count. We postulate that the antibodies produced in this disorder act either directly on megakaryocytes or their progenitors to impair platelet production or alternatively, that antibody-induced release of factor(s) from circulating platelets interferes with megakaryocytopoiesis. The primary action of corticosteroids is to improve platelet production. Whether this effect is achieved by interferring with antibody binding to marrow megakaryocytes; by preventing antibody induced release of platelet factors; or by modifying antibody production requires further study. These hypotheses will be explored using: 1) a newly developed quantitative system for in vitro assessment of marrow megakaryocytopoiesis; 2) peripheral platelet turnover measurements using radiolabeled autologous platelets; 3) quantitative platelets antibody assays to determine the type and amount of platelet-bound antibody (IgG including subclass specificity, IgM and complement); 4) imaging the Indium-labeled platelets to determine patterns of platelet sequestration; and 5) assays to quantitate release of platelet dense (ADP and ATP) or Alpha granule components (PF4 and BTG). Patients will be followed serially from diagnosis, through treatment with steroids and post-splenectomy to determine the effects of treatment on pathogenesis.